Smith G S, Nadig D E, Kokoska E R, Solomon H, Tiniakos D G, Miller T A
Department of Surgery, Saint Louis University School of Medicine, St. Louis, Missouri, 63104, USA.
J Surg Res. 1998 Dec;80(2):252-8. doi: 10.1006/jsre.1998.5441.
Acetaminophen (APAP) is a common analgesic and antipyretic compound which, when administered in high doses, has been associated with significant morbidity and mortality, secondary to hepatic toxicity. To date, the mechanism(s) whereby APAP induces liver injury remains to be delineated. This study investigated the potential role of neutrophils as contributors to liver injury in rats administered sublethal doses of APAP. Oral APAP administration (650 mg/kg) was associated with increases in serum alanine transaminase (ALT) levels indicating biochemical evidence of significant liver damage. Furthermore, histological analyses verified significant hepatocellular necrosis as well as enhanced myeloperoxidase staining in these liver specimens. However, if animals were pretreated with antineutrophil sera prior to APAP administration, neutrophil counts remained depressed, ALT levels were significantly decreased, and the degree of liver injury was attenuated on a histological level. Taken together these data suggest that neutrophils mediate, at least in part, the hepatotoxic effects of oral acetaminophen administration in rats.
对乙酰氨基酚（APAP）是一种常见的止痛和解热化合物，高剂量服用时，会因肝毒性导致显著的发病率和死亡率。迄今为止，APAP诱导肝损伤的机制仍有待阐明。本研究调查了中性粒细胞在给予亚致死剂量APAP的大鼠肝损伤中作为促成因素的潜在作用。口服APAP（650mg/kg）与血清丙氨酸转氨酶（ALT）水平升高有关，这表明有明显肝损伤的生化证据。此外，组织学分析证实这些肝脏标本中有明显的肝细胞坏死以及髓过氧化物酶染色增强。然而，如果在给予APAP之前用抗中性粒细胞血清对动物进行预处理，中性粒细胞计数仍会降低，ALT水平显著下降，并且在组织学水平上肝损伤程度减轻。综合这些数据表明，中性粒细胞至少在一定程度上介导了大鼠口服对乙酰氨基酚的肝毒性作用。
